Chromatographic assay or test device

ABSTRACT

A chromatographic assay or test device for detection and/or determination of an analyte in a test sample, comprises a base member, and a chromatographic medium located in or on said base member, the base member being provided with a receptacle to receive an applicator having the sample applied thereto, and the applicator being movable when located in said receptacle between a first position in which the applicator is out of fluid contact with the chromatographic medium, and a second position in which the applicator is in fluid contact with the chromatographic medium so as to apply a sample on the applicator to the chromatographic medium. In an alternative aspect, the test device comprises a base member, and a second member, at least one of the base member and the second member including a chromatographic medium, and the second member being slidably movable with respect to the base member from a first position to a second position.

FIELD OF THE INVENTION

[0001] This invention relates to a chromatographic assay or test devicefor detection and/or determination of an analyte in a sample, and in oneparticular embodiment it elates to a chromatographic assay device whichincorporates an immunoassay in a procedure known asimmunochromatography.

[0002] This invention has particular, but not exclusive, application inthe detection of analytes in biological samples such as blood, urine,faecal and saliva samples, and the like.

BACKGROUND OF THE INVENTION

[0003] Prior International Patent Applications Nos. PCT/US92/00425(WO92/21977) and PCT/US94/13982 (WO 95/16207) note that among the manyanalytical systems used for detection and/or determination of analytes,particularly analytes of biological interest, are chromatographic assaysystems. Among the analytes of biological interest frequently assayedwith such systems are:

[0004] 1. hormones, such as human chorionic gonadotropin (hCG),frequently assayed as a marker of human pregnancy;

[0005] 2. antigens, particularly antigens specific to bacterial, viral,and protozoan pathogens, such as Streptococcus, hepatitis virus,Giardia, feline leukaemia virus, tobacco mosaic virus, Salmonella, andPlasmodium;

[0006] 3. antibodies, particularly antibodies induced as a result ofinfection with pathogens, such as antibodies to the bacteriumHelicobacter pylori, to human immunodeficiency virus (HIV) and to felineimmunodeficiency virus (FIV);

[0007] 4. other proteins, such as haemoglobin, frequently assayed indeterminations of faecal occult blood, an early indicator ofgastrointestinal disorders such as colon cancer;

[0008] 5. enzymes, such as aspartate amino transferase, lactatedehydrogenase, alkaline phosphatase, and glutamate dehydrogenase,frequently assayed as indicators of physiological function and tissuedamage;

[0009] 6. drugs, both therapeutic drugs, such as antibiotics,tranquillisers and anticonvulsants, and illegal drugs of abuse, such ascocaine, heroin, and marijuana;

[0010] 7. vitamins; and

[0011] 8. environmental contaminants, such as pathogens, herbicides,pesticides, toxic residues, and the like.

[0012] Such chromatographic systems are frequently used by physiciansand medical technicians in the health field, and by agricultural andenvironmental professionals and technicians, for rapid point-of-care oron-site diagnosis, detection or monitoring of analytes of biologicalinterest. They are also increasingly used by patients themselves forat-home monitoring of a variety of therapeutic conditions and disorders.

[0013] Among the most important of such chromatographic systems are the“thin layer” systems in which a solvent moves as a solvent front acrossa thin, flat absorbent medium. Among the most important of tests thatcan be performed with such thin layer systems are immunoassays, whichdepend on the specific interaction between an antigen or hapten and acorresponding antibody. The use of immunoassays as a means of testingfor the presence and/or amount of clinically important molecules hasbeen known for some time.

[0014] As previously noted chromatographic techniques used inconjunction with immunoassays are known as immunochromatography. Ingeneral, this technique uses a disclosing reagent or particle that hasbeen linked to an antibody to the analyte to be assayed, forming aconjugate. This conjugate is then mixed with a specimen and, if theanalyte to be assayed is present in the specimen, the disclosingreagent-linked antibodies bind to the analyte to be assayed, therebygiving an indication that the analyte to be assayed is present. Thedisclosing reagent or particle can be identifiable by colour, magneticproperties, radioactivity, specific reactivity with another molecule, oranother physical or chemical property. The specific reactions that areemployed vary with the nature of the analyte being assayed and thesample to be tested.

[0015] Although useful, currently available chromatographic techniquesusing test strips have a number of drawbacks. Many samples, such asfaecal samples, contain particulate matter that can clog the pores ofthe chromatographic medium, greatly hindering the immunochromatographicprocess. Other samples, such as blood, contain cells and colouredcomponents that make it difficult to read the test. Even if the sampledoes not create interference, it is frequently difficult with existingchromatographic test devices to apply the sample to the chromatographicmedium so that the solvent front moves uniformly through thechromatographic medium to ensure that the sample reaches the area wherebinding is to occur in a uniform, straight-line manner.

[0016] Most immunochromatographic assay or test devices, because oftheir fixed and inflexible formats, are limited in their range ofdiagnostic applications. Most allow only unidirectional liquid flows andrequire that specimen or sample pre-treatments, such as antigenextraction, are carried out “off-board” or prior to addition to theassay or test device.

[0017] U.S. Pat. No. 5,415,944 (assigned to Quidel Corporation)discloses a closed test device which is adapted to allow “on-board”pre-treatment, or extraction, of a specimen on a swab. In this case, theswab is inserted into an extraction chamber, which is moulded as part ofthe housing of the test device. Extraction reagents are added to theswab and, after a period of time, unidirectional flow follows passivelyas the reagents migrate from the chamber to the wicking components ofthe immunochromatographic test system encased within the housing.

[0018] International Patent Application Nos. PCT/US92/04425 andPCT/US94/13982 (assigned to SmithKline Diagnostics, Inc.) mentionedabove, disclose testing systems involving sample preparation means ortest components placed on the opposing panels of an open two-panel testdevice. In this case, the test is only initiated or completed onbringing the two opposing panels together on closure of the test device.

[0019] It is an object of the present invention to provide an assay ortest device utilising a chromatographic assay format, more particularlyan immunochromatographic assay format, that is versatile as, well asbeing simple and economic to manufacture. In particular, it is an objectto provide an assay or test device that utilises a closed housing inassociation with a moveable or relocatable element that allowsmanipulation of liquid flows for initiation, modification and/orcompletion of the assay procedure.

SUMMARY OF THE INVENTION

[0020] In accordance with a first aspect of the present invention, thereis provided a chromatographic assay or test device for detection and/ordetermination of an analyte in a test sample, which comprises

[0021] (a) a base member, and

[0022] (b) a chromatographic medium located in or on said base member,

[0023] said base member being provided with a receptacle to receive anapplicator having said sample applied thereto, said applicator beingmovable laterally when located in said receptacle between a firstposition in which said applicator located in said receptacle is out offluid contact with said chromatographic medium, and a second position inwhich said applicator located in said receptacle is in fluid contactwith said chromatographic medium so as to apply a sample on saidapplicator to said chromatographic medium.

[0024] In another aspect, the present invention provides achromatographic assay or test device for detection and/or determinationof an analyte in a test sample, which comprises

[0025] (a) a base member, and

[0026] (b) a second member,

[0027] at least one of said base member and said second member includinga chromatographic medium, and said second member being movable laterallywith respect to the base member from a first position to a secondposition, wherein in said first position a sample to be assayed appliedto one of said base and second members is out of fluid contact with saidchromatographic medium, and in said second position said sample is influid contact with said chromatographic medium.

[0028] In yet another aspect, the present invention provides achromatographic assay or test device for detection and/or determinationof an analyte in a sample, which comprises:

[0029] (a) a base member, and

[0030] (b) a second member,

[0031] at least one of said base member and said second member includinga chromatographic medium, and said second member being movable laterallywith respect to the base member from a first position to a secondposition, wherein in said first position a part of the assay of a sampleusing said chromatographic medium is enabled, and in said secondposition another part of the assay of said sample using saidchromatographic medium is enabled.

[0032] Preferably, in each of the above aspects, the device of theinvention is an immunochromatographic assay device which includes animmunochromatographic medium.

[0033] The present invention also extends to a method for the detectionand/or determination of an analyte in a sample, characterised in that achromatographic assay or test device as broadly described above is usedin the method.

[0034] Throughout this specification and the claims which follow, unlessthe context requires otherwise, the word “comprise”, or variations suchas “comprises” or “comprising”, will be understood to imply theinclusion of a stated integer or group of integers but not the exclusionof any other integer or group of integers.

[0035] (b) a second member,

[0036] at least one of said base member and said second member includinga chromatographic medium, and said second member being movable laterallywith respect to the base member from a first position to a secondposition, wherein in said first position a sample to be assayed appliedto one of said base and second members is out of fluid contact with saidchromatographic medium, and in said second position said sample is influid contact with said chromatographic medium.

[0037] In yet another aspect, the present invention provides achromatographic assay or test device for detection and/or determinationof an analyte in a sample, which comprises:

[0038] (a) a base member, and

[0039] (b) a second member,

[0040] at least one of said base member and said second member includinga chromatographic medium, and said second member being movable laterallywith respect to the base member from a first position to a secondposition, wherein in said first position a part of the assay of a sampleusing said chromatographic medium is enabled, and in said secondposition another part of the assay of said sample using saidchromatographic medium is enabled.

[0041] Preferably, in each of the above aspects, the device of theinvention is an immunochromatographic assay device which includes animmunochromatographic medium.

[0042] The present invention also extends to a method for the detectionand/or determination of an analyte in a sample, characterised in that achromatographic assay or test device as broadly described above is usedin the method.

[0043] Throughout this specification and the claims which follow, unlessthe context requires otherwise, the word “comprise”, or variations suchas “comprises” or “comprising”, will be understood to imply theinclusion of a stated integer or group of integers but not the exclusionof any other integer or group of integers.

DETAILED DESCRIPTION OF THE INVENTION

[0044] The present invention particularly relates toimmunochromatographic test systems, but should not be seen as confinedto these systems.

[0045] Immunochromatographic test systems typically consist of anassemblage of some or all of the following components:

[0046] a test housing with ports for addition of specimen and/orreagents, or which acts as a window for reading of a test result.

[0047] a sample receiving member eg. an absorbent matrix. This componentmay also effect some sample pre-treatment (eg. extraction) or somephysical separation such as separating blood plasma from red cells.

[0048] a conjugate pad which contains an identifiable tag or labelconjugated to a specific binding partner to the analyte of interest.

[0049] a liquid conductive solid phase (eg. nitrocellulose, nylon, etc.)to, on, or in which is immoblised a second specific binding partner ofthe analyte.

[0050] a liquid absorbent material to act as a specimen and reagentsink.

[0051] other conductive membranes, reagent pads or supports as requiredfor the particular application.

[0052] In the various devices of the present invention, the base memberand the second member (where present) may be made of any suitablematerial including, for example, plastics materials such aspolycarbonate, polyethylene, Mylar, vinyl, cellophane and polystyrene,and well as water-proofed or water-resistant cardboard or similarmaterial. Preferably, the base and second members are made of laminatedcardboard that is sufficiently impervious to moisture to contain theliquids involved in the performance of the assay carried out by thedevice. Alternatively, the base and second members can be made of aplastic that is impervious to moisture, such as the polycarbonateplastic known as Lexan, polyvinylchloride, polypropylene, polyethylene,polystyrene, and the like.

[0053] Preferably the base member of the device of the present inventioncomprises upper and lower panels which are joined together to form atest housing. In the first aspect as broadly described above, thereceptacle to receive an applicator such as a swab, dipstick or othersample or specimen collection device is conveniently provided in a lowerpanel of the base member with the chromatographic medium being attachedto either the upper side of the lower panel or the lower side of theupper panel of the base member.

[0054] Where the device of this invention comprises a base member and asecond member which is movable with respect to the base member, the basemember preferably comprises upper and lower panels which are generallysquare or rectangular in shape and which are joined along oppositelongitudinal edges so as to form a test housing. Preferably, the secondmember then comprises a generally square or rectangular planar memberwhich is received within, and is slidably movable within, the testhousing between the upper and lower panels.

[0055] The chromatographic medium in the device is typically asubstantially planar strip, although this is not required in allapplications. Typically, the chromatographic medium comprises a solidphase which is generally rectangular in shape having first and secondends. Throughout this description, the term “first end” refers to theend in which liquid is first applied to chromatographic medium and theterm “second end” applies to the opposite end of the chromatographicmedium. The liquid applied at or near the first end of the solid phaseof the chromatographic medium can be, but is not necessarily, a sampleor a treated sample. The solid phase of the chromatographic medium iscomposed of an absorbent or porous material suitable as a medium forthin layer chromatography of analyte and analyte-antibody conjugates,such as nitro cellulose, nylon, rayon, cellulose, paper, silica ornon-woven or porous synthetic materials. This chromatographic medium canbe pretreated or modified as needed. Typically, this chromatographicmedium is translucent, so that coloured zones appearing on it can beviewed from either side.

[0056] In a number of devices according to the present invention,absorbers are in operable contact with one or both ends of thechromatographic medium. Such absorbers can be made of any suitablematerial that will hold a liquid, particularly an aqueous liquid,sufficiently that the liquid can be drawn through the chromatographicmedium and accumulated in the absorber. Typically materials for suchabsorbers include, but are not limited to, filter paper.

[0057] Further description of elements common to devices according tothe present invention for the performance of chromatographic assays ortests are fully described in International Patent Application Nos.PCT/US92/04425 and PCT/US94/13982 mentioned above, the contents of whichare incorporated herein by reference.

[0058] In a first aspect, the present invention provides a device whichcomprises a base member which is provided with a receptacle to receivean applicator having a test sample applied thereto. Suitably, such areceptacle is formed as an elongate well in the base member shaped toaccept a swab, dipstick or similar collection device having a testsample applied thereto. The elongate well is suitably constructed thatthe applicator or collection device can be received within the elongatewell in a first position out of liquid contact with the chromatographicmedium of the test device, and at this first position the test sample onthe applicator or collection device may be treated with appropriateextraction or other reagents prior to the applicator or collectiondevice being moved within the elongate well to a second position inwhich it is in liquid contact with the chromatographic medium so as toapply the test sample to the chromatographic medium.

[0059] In particular embodiments, the base member in the device of thepresent invention may comprise separate upper and lower panels, with thechromatographic medium being attached to the upper panel and the lowerpanel being formed with an integral elongate well, for example by vacuumforming the lower panel from a suitable plastic material such aspolyvinyl chloride. Alternatively, the lower panel may be formed of asuitable cardboard or plastic with a punched aperture defining asuitable elongate well, with a flexible fluid impervious membraneoverlay being provided over the punched hole so as to define theelongate well. A preferred device in accordance with this aspect of theinvention is more fully described with reference to FIGS. 1 and 2 below.

[0060] In other aspects of the present invention as broadly describedabove, the device comprises a base member and a second member with thesecond member being movable with respect to the base member from a firstto a second position. Preferably, this movement is a sliding movement ofthe second member with respect to a test housing which comprises thebase member as broadly discussed above. Preferably, also the base memberprovides an elongate housing and the second member is an elongate memberwhich is slidably movable between the first and second positions withinthis housing. Particular embodiments of these aspects of the presentinvention are described in detail in FIGS. 3-8 below.

BRIEF DESCRIPTION OF THE DRAWINGS

[0061] Various features of a number of embodiments of the presentinvention are illustrated by way of example in the accompanying drawingswhich are included by way of illustration, and not limitation of thisinvention. In the accompanying drawings:

[0062] FIG. 1 comprises (a) a plan view and (b) a cross sectional viewof a chromatographic assay or test device in accordance with a firstaspect of the present invention.

[0063] FIG. 2 is an exploded view of an alternative embodiment of thebase member of the device of FIG. 1 +L.

[0064] FIG. 3 comprises (a) plan views and (c) side elevations of achromatographic assay or test device in accordance with a second aspectof the present invention.

[0065] FIG. 4 comprises a series of plan views of another embodiment ofa device in accordance with the second aspect of the invention.

[0066] FIG. 5 comprises (a) plan views and (c), (d) side elevations of achromatographic assay or test device in accordance with a third aspectof the present invention.

[0067] FIG. 6 shows plan views of another embodiment of a device inaccordance with the third aspect of the invention.

[0068] FIG. 7 depicts a further embodiment of a chromatographic assay ortest device in accordance with this invention which is particularlysuited for antigen assay procedures which use blood as the testspecimen.

[0069] FIG. 8 shows diagrammatically yet another embodiment of an assayor test device in accordance with this invention.

[0070] Referring firstly to FIG. 1 +L, there is shown an assay or testdevice in which an applicator, particularly a specimen collection devicesuch as a swab or dipstick, when fully inserted, effects a liquidconducting bridge between the applicator and a chromatographic teststrip, particularly an immunochromatographic test strip, therebyinitiating the development of the test. FIG. 1 +La is a plan view of atest device of this type which comprises an base member 1 consisting ofupper and lower panels forming a test device housing and containing awindow 2 for reading of the test result. The housing also contains anopening 3 in the upper panel thereof for insertion of a swab, dipstickor other specimen collection device. An immunochromatographic test strip5 is located on the underside of the upper panel of the base member 1and is covered by a protective barrier 6 leaving exposed a first end 8of the test strip 5. An elongate well or reagent reservoir 4 is formedin the lower panel of the base member 1.

[0071] FIG. 1 +Lb shows a cross section along the line A-A of the deviceof FIG. 1 +La, with a swab 7 fully inserted into the well or reagentreservoir 4 of the device.

[0072] The closed test device shown in FIGS. 1 +La and 1 +Lb comprises atest device housing comprising the upper panel which houses oraccommodates the immunochromatographic test strip 5 enclosed at all butits first end or origin 8 by the liquid impermeable protective barrier6. The lower panel of the test device housing has an elongate welladapted to receive a swab, dipstick or other specimen collection devicevia opening 3 in the housing. The elongate well may receive reagents,via the opening 3, before, during or after insertion of the swab,dipstick or other specimen collection device. Alternatively, theelongate well may act as a reagent reservoir by having appropriatereagents prepackaged within the well by means of flexible packaging andfrangible seals. In this alternative, insertion of the swab, dipstick orother specimen collection device into the elongate well would rupturethe seal(s), thus exposing the specimen collection device to thereagent(s).

[0073] In many cases, it is beneficial to expose a sample on a specimencollection device to the appropriate reagent(s) for some period of timeprior to initiation of the test development, for example, to effectsolubilisation or extraction of diagnostically significant antigens. Thetest device shown in FIGS. 1 +La and b is designed so that partialinsertion of the specimen collection device 7 into the elongate well 4locates the device 7 at a first position enabling reagent addition tothe test sample without the initiation of the test development. Afterallowing time for extractions/solubilisation of antigens in the sample,full insertion of the device 7 to a second position as shown in FIG. 1+Lb then establishes liquid contact between the device 7 and the firstend or origin 8 of the immunochromatographic test strip 5. Testdevelopment is thus initiated and continues until reagent or specimendepletion, or until liquid contact is broken by partial (or full)withdrawal of the device 7.

[0074] FIG. 2 shows an alternative design of the base member of thedevice of FIG. 1 +L. In the alternative device, the housing comprisesupper and lower panels 21 and 26, respectively. As shown in FIG. 2+L(a), the upper panel 21 has a hinged “door” 24 for insertion of aswab, dipstick or other specimen collection device and for addition ofreagent(s), together with a window 25 for reading of the test results.FIG. 2 +L(b) shows the underside of the upper panel 21 which has affixedthereto an immunochromatographic test strip with all but its samplereceiving first end or origin 22 protected by a moisture impermeableprotective barrier 23. Upper panel 21 is preferably made of laminatedcardboard or plastic, and is designed to be mass produced by dye-cuttingand printing, with component lay down by a high-speed, fully automatedassembly process. FIG. 2 +L(c) shows the lower panel 26, with integralelongate well 27. This lower panel is preferably vacuum formed from asuitable plastics material, such as polyvinyl chloride. Alternatively, alaminated cardboard or plastic panel may be used, with a punched holedefining a suitable elongate well, and a flexible moisture impermeablemembrane overlaying the punched hole to form the elongate well. Aspreviously described, the elongate well may also be adapted to housingpre-packaged reagent(s) so that insertion of a specimen collectiondevice liberates the reagents to the sample on the specimen collectiondevice.

[0075] Assembly of the device shown in FIG. 2 would consist of bindingthe upper panel to the lower panel. The lower panel would preferably beformed in situ and bound to the upper panel using a high speed fullyautomated form/fill/seal machine, as used for blister packaging manyinexpensive, mass produced consumer products.

[0076] In the embodiments of the invention shown in FIGS. 3-8 , thecomponents of a closed test device are moveable with respect to otheranother so that they may be repositioned during the course of a test(including for initiation and at completion) in order to manipulate orcontrol application of a test sample and various liquid flows, and hencethe development of the test. Accordingly, the device of the presentinvention, by allowing flow control through the repositioning ofcomponents within a closed test device, allows a wide range of testprocedures to be simply and efficiently completed.

[0077] FIG. 3 illustrates a closed assay or test device with utilises aperiod of static preincubation of the sample with conjugate prior tocommencement of reagent flow and capture in a chromatographic medium.

[0078] FIG. 3 +L(a) shows a closed test device comprising a housing orbase member including upper panel 37 which includes sample addition port31 together with window 34 for reading the results of the assay or test.The housing or base member also comprises lower panel 38 as shown inFIG. 3 +L(b)(ii). A second member in the form of movable element 36 isformed as a sliding panel movable from a first position to a secondposition with respect to the base member. FIG. 3 +L(b)(i) shows theunderside of the upper panel 37 and shows conjugate pad 32 affixed tothe underside of the upper panel 37 below the sample addition port 31,together with an absorbent pad 35. Immunochromatographic test strip 33is affixed to the second member 36 which is movable from a firstposition (solid lines) to second position (broken lines).

[0079] FIG. 3 +L(c)(i) is a side elevation of the device of FIG. 3 +Lawith the components in the first position. Sample is added to theconjugate pad 32 through the port 31 and reconstitutes the conjugate. Noflow is possible so a pre-incubation step between the conjugate andanalyte in the sample can take place. FIG. 3 +L(c)(ii) shows thecomponent of the device in the second position in which movable secondmember 36 has been moved so that the origin of the immunochromatographictest strip 33 is in liquid-contact with the sample/conjugate mixture inconjugate pad 32. Flow of reagent and test development may now takeplace, via the immunochromatographic test strip 33 (which willincorporate a capture band) to the absorbent 35.

[0080] As described above, preferred designs in this aspect of thepresent invention use a three-panelled base member or housing in whichthe upper and lower panel are attached in such a way as to control andguide a movable middle panel or second member. The test components maybe affixed to any of the panels in any manner required to meet therequirements for completing the particular test.

[0081] FIG. 4 illustrates an alternative embodiment of the test deviceshown in FIG. 3 based on the test requirements and component placementspreviously described in FIG. 3 enabling a period of pre-incubation of asample with a conjugate before commencement of flow/capture.

[0082] FIG. 4 +L(a) shows the test device 41 in the first or closedposition. The base member of the device comprises an upper panel 413having a window 42 through which result lines 45 on the solid phase 47may be observed. The specimen port 44 is closed in the first position,and an instruction window 43 may be blank or have a printed instructionabout proceeding to the second position of the test.

[0083] Pressure applied at point 46 causes displacement of the movablepanel 410 forming the second member to the second position as shown inFIG. 4 +L(b). In this position, the specimen port 44 is open and theinstruction window 43 may have an instruction about addition of the testsample to the port 44. The result window 42 is closed by the slidingpanel 410 while the device is in the second position.

[0084] FIG. 4 +L(c) shows the underside of the upper panel 413 whichtogether with lower panel 412 makes up the base member of the device.FIG. 4 +L(d) shows the upper side of the lower panel 412 with animmunochromatographic test strip 49 affixed thereto. Test strip 49consists of the solid phase 47 as well as a stop 48, which together witha similar stop 415 shown in FIG. 4 +L(e), acts to prescribe the range ofdisplacement of the movable panel 410.

[0085] FIG. 4 +L(e) shows the underside of the movable middle panel 410.A clear plastic support strip 416 pre-laminated with a stop 415,conjugate pad 417 and absorbent 419 is affixed to the panel. The panelhas a window 418 (as shown in dotted outline) which coincides with thewindow opening 42 of the upper panel when the test is in the firstposition. Conjugate pad 417 is accessed by a hole or perforation(dotted) in panel 410 and a corresponding hole or perforation in supportstrip 416. The upper side of the movable panel 410 may be printed withinstructions placed to appear in the instruction window 43 in the firstand second positions. The upper and lower panels 413 and 412 may bejoined by tape at the longitudinal edges thereof so that the middlepanel 410 remains free to slide within the base member of the device.This format is designed to be suited to inexpensive, high speed, fullyautomated assembly procedures, for example, the panels may be die cut,printed and the relevant components affixed in one continuous operation.At this stage, the panels may be stacked and stored in a magazine untilrequired for completion of assembly. The three panels may then be fedfrom the magazines to a nest on a conveyor belt, the edges taped, andthe assembled device packaged into a hermetically sealed bag in onefurther operation.

[0086] The test procedure for a device as shown in FIG. 4 +L, is firstlyto move the movable middle panel 410 to the second position and addsample to the reagent port 44. In this position, the conjugate pad 417,accessed through the specimen port 44 and corresponding holes orperforations in panel 410 and support strip 416, is disconnected fromthe solid phase 47 so no flow/capture occurs. After a period forpre-incubation of the sample with the conjugate in pad 417, the movablepanel 410 is returned to the first position. This establishes contactbetween the conjugate pad 417 and the solid phase 47 of theimmunochromatographic test strip 49, allowing development of the assayor test. The result may be read through the result window 42.

[0087] FIG. 5 illustrates another embodiment of the device of thepresent invention which includes the use of forward flow of sample alongthe solid phase for capture of the analyte in the sample, followed byreverse flow along the solid phase for labelling. The ability to conductforward and reverse flows along the solid phase is an advantage inseveral assay types. For example:

[0088] Heavily pigmented specimens (eg. lysed blood), obscure the visualassessment of a developing colour at the detection (capture) line of thesolid phase. The ability to reverse the flow with, for example, a cleanwash solution enables the result to be clearly seen.

[0089] In some test applications, the conjugate bound to the analyte maysterically hinder the efficient capture of the complex at the captureline.

[0090] For serological assays, the specific antibody of interest may becaptured on forward flow and labelled on reverse flow. Interference fromthe vast excess of non-specific antibody prevents the use of other assayconfigurations for serological assays.

[0091] FIG. 5 +La shows an embodiment of a device utilising both forwardand reverse flows and shows the upper face of upper panel 59 of the basemember forming a test housing. The upper panel includes a specimen port51, a window 52 for confirming flow of reagent, a window 53 for readingthe results of the test or assay together with a reagent port 54.

[0092] FIG. 5 +L(b)(i) shows the lower face of the upper panel 59 of thetest housing which has affixed thereto a sample or specimen pad 55, anabsorbent pad 56 and a reagent pad 57. FIG. 5 +L(b)(ii) shows movementof a movable second member 512 having the immunochromatographic solidphase 58 affixed thereto, from a first position to a second positionwith respect to the lower panel 511 of the base member of the testhousing.

[0093] FIGS. 5 +L(c) and (d) show the positioning of the movable member512 with respect to the base member or test housing and reagent flows inthe first and second positions, respectively. With the components in thefirst position, forward flow of reagents and capture of the analyte inthe sample is enabled. The sample is added via the specimen port 51 tothe specimen pad 55. Flow of specimen occurs along the solid phase 58 inthe direction shown by arrows into the absorbent pad 56 (the flow may beobserved via a window 52 and may continue until reagent/specimendepletion or until the components are moved to the second position). Inthe second position, reverse flow of reagents provides for labelling.Liquid is added through the reagent port 54 to reconstitute conjugate inthe conjugate pad 57. Conjugate flows along the solid phase 58 into theabsorbent 56 and the result may be observed through the window 53.

[0094] As noted above, this assay format is particularly suitable forserological assays. For example, for the detection of antibodies to HIVin human blood, the procedure using this device would be as follows:

[0095] (i) With the components in the first position human blood isadded via the port 51 to a blood separation membrane 55. Plasma flowsvia the solid phase 58 and antibodies against HIV bind to a band ofHIV-specific antigen immobilised in the solid phase at Y.

[0096] (ii) After a specified flow time or distance, the components aremoved to the second position. Liquid (eg. buffer) added through port 57causes conjugate (anti-human IgG) conjugated to a visible label to flowdown the solid phase 58 and bind to any human antibodies captured at Y.An accumulation in colour at Y is observed through the window 53.

[0097] FIG. 6 illustrates a variant of the format of FIG. 5 and thecomponent placements and reagent flow paths are as described with regardto FIG. 5 . Device 64 is issued with the second member 65 in its firstposition with respect to the base member or test housing 66. To conducta test, the member 65 is moved to the second position (defined byinternal stops), and specimen is added to the specimen port 61 inaccordance with instructions provided in the instruction window (S).Reagent is added to the reagent port 62 in accordance with instructionsgiven in instruction window (R) in order to reconstitute conjugatecontained in the conjugate pad under the port 62. Member 65 is thenreturned to the first position with respect to the test housing 66 andby this action the ports and instruction windows close, the specimen padis disconnected from the solid phase, the conjugate pad makes contactwith the solid phase and reverse flow labelling and test developmentflow as described with respect to FIG. 5 . The test result is then readin the window 63.

[0098] The device shown in FIG. 7 is particularly adapted for use inantigen detection procedures, for example in detection of antigensspecific to bacterial, viral and protozoan pathogens in blood samples.The test device of FIG. 7 comprises upper and lower panels, 710 and 711,shown in FIGS. 7 +La and 7 b respectively, together with a sliding panel712, shown in FIGS. 7 +Lc and 7 d which slides within a test housingformed by the upper and lower panels which are joined along thelongitudinal edges thereof to form this housing. Upper panel 710includes a reagent port 78 and window 79 for observing the results ofthe test development. Test strip 71 is located on the lower panel 711and comprises an absorbent pad 72 and a conjugate pad 73 with the solidphase of the immunochromatographic medium 74 located between these pads.Test strip 71 is overlaid with a clear protective membrane 75 whichprotects the absorbent pad 72 from wetting by plasma from a blood sampleapplied to the assay device when the sliding panel 712 is returned tothe first position for development of the test result. Protectivemembrane 75 is provided with a hole or perforation therein coincidingwith the conjugate pad 73.

[0099] As shown in FIGS. 7 +Lc + l and 7 +Ld, sliding panel 712 isprovided with a reagent pad 77 together with a blood separation module76, shown in greater detail in S. 7 +Le + l and 7 f. Referring to FIGS.7 +Le + l and 7 +Lf, the blood separation module comprises a backingstrip having a port 714 formed therein. Port 714 is covered by anabsorbent matrix and a blood separation membrane 715, preferably a multilayer separation membrane such as a MPS membrane (available fromSpectral Diagnostics Inc., Toronto, Ontario, Canada).

[0100] In the use of the device shown in FIG. 7 +L, sliding panel 712 ismoved to the second position as shown in FIG. 7 +Lc, and a blood sampleis added to the device through the open port 78 in the upper panel 710.Plasma is separated from the blood sample by separation module 76, andas the separation module 76 is in contact with the conjugate pad 73 inthis position, plasma permeates the conjugate pad 73. After a suitabletime, for example 1 minute, the sliding panel 712 is moved to the firstposition where the separation module 76 moves over the absorbent pad 72(but the absorbent pad 72 is protected from wetting by plasma from theseparation module 76 by the protective membrane 75). In this position,the reagent pad 77 contacts the conjugate pad 73. An appropriate amountof developer reagent is added to the reagent pad 77 through the openport 78 so that the added reagent displaces the conjugate/plasma mixturealong the solid phase 74 to the absorbent pad 72. After an appropriatetime, the test result is observed through the window 79.

[0101] FIG. 8 shows diagrammatically a further embodiment of the assayor test device of the present invention which operates on similarprinciples to the device shown in FIG. 5 +L, however whereas the deviceof FIG. 5 operates using both forward and reverse flow in sequence, withcapture on forward flow followed by labelling on reverse flow, thedevice of FIG. 8 is designed to enable these sequential assays to beconducted using forward flow only, that is with the sample and theconjugate being applied in sequence to the same end or origin of thechromatographic medium.

[0102] The device shown in FIG. 8 comprises a base member of testhousing made up of an upper panel 86 and lower panel 87. Upper panel 86is provided with appropriate ports and windows for addition of reagentsand samples and for observing test results. On the underside of upperpanel 85 are located a sample application pad 84, which may comprise ablood separation module as described with reference to FIG. 7 above, anda conjugate pad 85. The second member of the device of FIG. 8 +L, whichis movable with respect to the test housing comprising panels 86 and 87between first and second positions as shown, comprises a chromatographicmedium 81 in liquid contact at one end with an absorbent pad 82 which isoverlaid with a liquid-impermeable barrier membrane 83.

[0103] In use of the device shown in FIG. 8 +L, the device is initiallyset up in the first position as shown where the sample application pad84 is in contact with the first end or origin of the chromatographicmedium 81. The sample is applied to the application pad 84 and flows upthe chromatographic medium into the absorbent pad 82. After anappropriate period of time, the second member is moved to the secondposition as shown where the conjugate pad 85 is brought into contactwith the first end of origin of the chromatographic medium 81. Sampleapplication pad 84 is positioned above the absorbent pad 82 and sincethe absorbent pad is overlaid with the barrier membrane 83, sample pad84 is out of liquid contact with the chromatographic medium in thisposition. Addition of reagent to conjugate pad 85 applies conjugate tothe first end or origin of the chromatographic medium 81 and enablesflow of conjugate along the chromatographic medium for development ofthe assay.

[0104] It will be appreciated by a person skilled in this art thatwhilst a number of particular embodiments of the present invention havebeen described in detail above and are shown in the accompanyingfigures, many variations and alterations may be made to theseembodiments without departing from the spirit and scope of the presentinvention as broadly described above. Accordingly, the present inventionextends to all embodiments of the invention which fall within the broadscope and spirit of the invention as described herein.

1. A chromatographic assay or test device for dtection and/ordetermination of an analyte in a test sample, which comprises (a) a basemember, and (b) a chromatographic medium located in or on said basemember, said base member being provided with a receptacle to receive anapplicator having said sample applied thereto, said applicator beingmovable laterally when located in said receptacle between a firstposition in which said applicator located in said receptacle is out offluid contact with said chromatographic medium, and a second position inwhich said applicator located in said receptacle is in fluid contactwith said chromatographic medium so as to apply a sample on saidapplicator to said chromatographic medium.
 2. A chromatographic assay ortest device for detection and/or determination of an analyte in a testsample, which comprises (a) a base member, and (b) a second member, atleast one said base member and said second member including achromatographic medium, and said second member being movable laterallywith respect to the base member from a first position to a secondposition, wherein in said first position a sample to be assayed appliedto one of said base and second members is out of fluid contact with saidchromatographic medium, and in said second position said sample is influid contact with said chromatographic medium.
 3. A chromatographicassay or test device for detection and/or determination of an analyte ina sample, which comprises: (a) a base member, and (b) a second member,at least one of said base member and said second member including achromatographic medium, and said second member being movable laterallywith respect to the base member from a first position to a secondposition, wherein in said first position a part of the assay of a sampleusing chromatographic medium is enabled, and in said second positionanother part of the assay of said sample using said chromatographicmedium is enabled.
 4. An assay or test device according to claim 1,claim 2 or claim 3 which comprises an immunochromatographic medium. 5.An assay or test device according to claim 1, claim 2 or claim 3,wherein the base member and/or the second member, when present,comprises a material selected from plastics materials, water-proofed orwater-resistant cardboard or similar material.
 6. An assay or testdevice according to claim 1, claim 2 or claim 3, wherein saidchromatographic medium comprises a substantially planar strip.
 7. Anassay or test device according to claim 6, wherein said chromatographicmedium comprises an absorbent or porous material selected fromnitrocellulose, nylon, rayon, cellulose, paper, silica and non-woven orporous synthetic materials.
 8. An assay or test device according toclaim 1, wherein said base member comprises upper and lower panels whichare joined together to form a test housing, and said receptacle toreceive an applicator is formed in said lower panel.
 9. An assay or testdevice according to claim 8, wherein said receptacle comprises anelongate well adapted to receive an applicator selected from a swab,dipstick or other sample or specimen collection device.
 10. An assay ortest device according to claim 9 wherein said elongate well comprises areagent reservoir.
 11. An assay or test device according to claim 8,wherein said chromatographic medium is attached either to the upper sideof the lower panel of the base member, or to the lower side of the upperpanel of the base member.
 12. An assay or test device according to claim2 or claim 3, wherein said base member comprises upper and lower panelswhich are generally square or rectangular in shape and which are joinedalong opposite longitudinal edges to form a test housing.
 13. An assayor test device according to claim 12, wherein said second membercomprises a generally square or rectangular planar member which isreceived within, and is slidably movable within, said test housingbetween the first and second positions of said second member.
 14. Anassay or test device according to claim 13, wherein animmunochromatographic test strip is located on said second member, andin said first position said test strip is out of fluid contact with asample or conjugate pad located on the underside of the upper panel ofthe test housing, while in said second position said test strip is influid contact with said sample or conjugate pad.
 15. An assay or testdevice according to claim 13, wherein an immunochromatographic teststrip is located on the upper side of the lower panel of the testhousing, and in said first position said test strip is in fluid contactwith a sample or conjugate pad located on said second member, while insaid second position said test strip is out of fluid contact with saidsample or conjugate pad.
 16. An assay or test device according to claim13, wherein an immunochromatographic test strip is located on saidsecond member, and said second member is movable from said firstposition in which forward flow of test reagents on said test strip isenabled to said second position in which reverse flow of test reagentsis enabled.
 17. An assay or test device according to claim 13, whereinan immunochromatographic test strip is located on said second member,and said second member is movable from said first position in whichcapture of an analyte in a test sample on said test strip is enabled tosaid second position in which labelling of captured analyte is enabled.18. A method for the detection and/or determination of an analyte in asample, characterised in that a chromatographic assay or test deviceaccording to any of claims 1 to 17 is used.